CPC14 A truly VEXing diagnosis
Authors: Fiona Lynch, Kieran Murray, Niamh Leonard, Muriel Sadlier
Journal: British Journal of Dermatology (2023)

Abstract A 50-year-old man with a background of prostate cancer was admitted with fever, weight loss, polyarthritis, symptomatic anaemia and raised inflammatory markers. Multiple tender indurated violaceous plaques on the trunk and limbs were suggestive of Sweet syndrome. Skin biopsies revealed a neutrophilic dermal infiltrate and a pandermal vasculitis affecting small vessels. Laboratory screening (including rheumatoid factor, anticyclic citrullinated peptide, antinuclear antibody, antineutrophil cytoplasm antibodies, HIV, hepatitis B and C serology, antiphospholipid antibodies and cryoglobulins) was negative. Upper and lower endoscopies and gastrointestinal biopsies were normal. Biopsy of an axillary lymph node revealed reactive changes only. Computed tomography (CT) of the thorax, abdomen and pelvis showed sacroiliitis. A diffuse low signal on T1-weighted magnetic resonance imaging of his spine was suggestive of conversion of fatty marrow to red marrow. His cutaneous findings resolved fully with oral prednisolone 0.5 mg kg−1; however, he had ongoing transfusion-dependent anaemia and arthritis. Infliximab was started for presumed ankylosing spondylitis by rheumatology without improvement. Six months later, he was readmitted with multifocal ulceration of both feet. Histology demonstrated a leucocytoclastic vasculitis. He developed haemoptysis and chest pain. CT of the thorax showed multifocal, bilateral, ground–glass change consistent with pulmonary vasculitis. Bone marrow biopsy revealed hypercellular marrow with markedly increased granulopoiesis. A pathogenic missense mutation in UBA1 (c121A.G; pMet41Val) was found on next-generation sequencing of the bone marrow aspirate (Leeds Cancer Centre). Somatic variants at this codon have been implicated in vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome (Beck DB, Ferrada MA, Sikora KA et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med 2020; 383:2628–38). First described in 2020, VEXAS syndrome is a somatic monogenic autoinflammatory disorder of adulthood. Affected patients develop predominantly inflammatory and haematological symptoms. Cutaneous findings have been reported in up to 89% of cases (Georgin-Lavialle S, Terrier B, Guedon AF et al. Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients. Br J Dermatol 2022; 186:564–74) and include neutrophilic dermatosis, vasculitis, urticaria, angioedema, erythematous papules and chondritis. Systemic manifestations are protean, but fever of noninfectious origin, weight loss, and ocular and pulmonary manifestations are most prevalent. Fifty per cent of patients with VEXAS have myelodysplastic syndrome (Georgin-Lavialle et al.). In our case, persistent haematological abnormalities coupled with multisystem inflammation (arthritis, vasculitis) prompted testing for VEXAS syndrome. This novel condition should be considered when assessing adult patients with neutrophilic dermatosis or cutaneous vasculitis who manifest other autoinflammatory phenomena. He was commenced on tocilizumab but, despite this, has ongoing acral vasculopathy.